EP0127529A2 - Aminocyclic N-oxide derivatives, process for their preparation and their therapeutical use - Google Patents
Aminocyclic N-oxide derivatives, process for their preparation and their therapeutical use Download PDFInfo
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- EP0127529A2 EP0127529A2 EP84401032A EP84401032A EP0127529A2 EP 0127529 A2 EP0127529 A2 EP 0127529A2 EP 84401032 A EP84401032 A EP 84401032A EP 84401032 A EP84401032 A EP 84401032A EP 0127529 A2 EP0127529 A2 EP 0127529A2
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- alkyl
- alkyloxy
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- compounds
- equatorial
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- 0 Cc1cc(*)cc(*)c1* Chemical compound Cc1cc(*)cc(*)c1* 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/94—Oxygen atom, e.g. piperidine N-oxide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/14—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
Definitions
- the present invention relates to new N-oxides of aminocyclic derivatives, their preparation process and their application in therapy.
- the oxidation is carried out by using a peracid such as metachloro-perbenzoric acid or a peroxide such as hydrogen peroxide; when using metachloroperbenzoic acid, it is preferably carried out in an aprotic solvent such as methylene chloride and at low temperature such as 0 ° C. and when using hydrogen peroxide, it is preferably carried out at reflux in a aprotic solvent such as acetonitrile.
- a peracid such as metachloro-perbenzoric acid or a peroxide such as hydrogen peroxide
- the separation of forms (la) and (Ib) can in particular be carried out by column chromatography, preferably by liquid chromatography on a silica column, at high or medium pressure, the separate forms being identified by their spectral properties, using NMR spectra
- the compounds according to the invention have been studied in laboratory animals and have shown activity on the central nervous system, in particular a neuroleptic action.
- mice have been demonstrated in mice, in particular by the test of antagonism to rectifications with apomorphine carried out according to the protocol described by G. GOURET and Coll. in J. Pharmacol. (Paris) ( 1973 ), 4, 34 1 .
- the difference between the toxic doses and the active doses allows the use of the compounds (I) as medicaments, in particular in the treatment of mental disorders, in particular as neuroleptics.
- the present invention therefore also relates, as medicaments, to the compounds of formula (I) which are pharmaceutically acceptable.
- the invention extends to pharmaceutical compositions containing, as active principle, at least one of the medicaments defined above, in combination with a pharmaceutically acceptable vehicle.
- compositions can be administered in particular (a) orally in the form of tablets, dragees or capsules each containing up to 300 mg of active principle (up to 8 tablets, dragees or capsules per day) or in the form of a solution containing 0.1 to 1% of active ingredient (up to 60 drops, one to three times a day) or (b) parenterally in the form of injectable ampoules each containing up to 100 mg of active ingredient (up to 8 vials per day).
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Description
La présente invention a pour objet de nouveaux N-oxydes de dérivés aminocycliques, leur procédé de préparation et leur application en thérapeutique.The present invention relates to new N-oxides of aminocyclic derivatives, their preparation process and their application in therapy.
Plus précisément, les nouveaux composés selon l'invention répondent à la formule :
- a) un groupe pyrimidinique de formule :
- b) un groupe aromatique de formule :
R3 pouvant en outre représenter un groupe NH2 ou NH-alkyl en C1-C4 quand R4 = halogène et un atome d'hydrogène quand R4 représente un groupe OH ou alkyloxy en C1-C4; - c) un groupe aromatique de structure :
- d) un groupe aromatique de structure :
- a) a pyrimidine group of formula:
- b) an aromatic group of formula:
R 3 can also represent an NH 2 or NH-C 1 -C 4 alkyl group when R 4 = halogen and a hydrogen atom when R 4 represents an OH or C 1 -C 4 alkyloxy group; - c) an aromatic group with a structure:
- d) an aromatic group with a structure:
Il est à noter que les composés selon l'invention :
- - se présentent sous la forme axiale (Ia):
- - sont constitués par un mélange de la forme axiale (Ia) et de la forme équatoriale (Ib).
- - are in the axial form (I a ):
- - consist of a mixture of the axial shape (Ia) and the equatorial shape (Ib).
Les composés de formule (I) selon l'invention peuvent être obtenus par oxydation des composés de formule :
Avantageusmpnt, on réalise l'oxydation par mise en oeuvre d'un peracide tel que l'acide métachloro- perbenzorque ou d'un peroxyde tel que l'eau oxygénée; quand on utilise l'acide métachloroperbenzoï- que, on opère de préférence dans un solvant aprotique tel que le chlorure de méthylène et à basse température telle que 0° C et quand on utilise l'eau oxygénée, on opère de préférence au reflux dans un solvant aprotique tel que l'acétonitrile.Advantageously, the oxidation is carried out by using a peracid such as metachloro-perbenzoric acid or a peroxide such as hydrogen peroxide; when using metachloroperbenzoic acid, it is preferably carried out in an aprotic solvent such as methylene chloride and at low temperature such as 0 ° C. and when using hydrogen peroxide, it is preferably carried out at reflux in a aprotic solvent such as acetonitrile.
La séparation des formes (la) et (Ib) peut être notamment réalisée par chromatographie sur colonne, de préférence par chromatographie liquide sur colonne de silice, à haute ou moyenne pression, les formes séparées étant identifiées par leurs propriétés spectrales, notamment à l'aide des spectres de R.M.N.The separation of forms (la) and (Ib) can in particular be carried out by column chromatography, preferably by liquid chromatography on a silica column, at high or medium pressure, the separate forms being identified by their spectral properties, using NMR spectra
Les composés de formule (II) sont quant à eux obtenus conformément aux protocoles opératoires décrits dans les brevets français 2 446 823, 2 476 088 et 2 493 848.The compounds of formula (II) are obtained in accordance with the operating protocols described in French patents 2,446,823, 2,476,088 and 2,493,848.
Les préparations suivantes sont données à titre d'exemple non limitatif pour illustrer l'invention.The following preparations are given by way of nonlimiting example to illustrate the invention.
①A une solution de 6,5 g deβ-(diméthoxy-2,3) benzoylamiro-3 N-benzyl aza-8 bicyclo [3.2.1] octane (II) dans 150 ml de chlorure de méthylène refroidie à 0° C, on ajoute 3,6 g d'acide métachloroperbenzofque ; on laisse 10 minutes en contact, puis on lave à l'aide de NaOH 1 N, décante, sèche la phase organique sur sulfate de sodium, filtre et évapore le filtrat. L'huile brute obtenue est chromatographiée sur une colonne de silice (chromatographie liquide à moyenne pression). Par élution à l'aide du mélange chlorure de méthylène 95 % - méthanol 5 %, on obtient (a) 4,5 g (66 %) du N-oxyde axial (la) (numéro de code 1) que l'on recristallise dans le pentane:
- . Point de fusion : 210° C
- . Formule brute : C23H28N2O4
- . Poids moléculaire : 396,47
- . Spectre de R.M.N. (à 250 MHz ; CD3OD) δ ppm =
- . entre 7,05 et 7,65, m, (8 protons benzéniques et CONH)
- . 4,5, m, proton axial en 3
- . 4,42, s, -CH2 benzylique
- . 3,82 et 3,88, s, 2 CH30
- . 3,53, s, 2 protons tropaniques en 1 et 5
- . 2,5, m, protons tropaniques axiaux en 2 et 4 et 2 protons tropaniques en 6 et 7
- . 2,25, m, 2 protons tropaniques en 6 et 7
- 1,92, m, 2 protons tropaniques équatoriaux en 2 et 4
puis (b) 1,2 g (17 %) du N-oxyde équatorial (Ib) (numéro de code 2) que l'on recristallise dans l'éther éthylique: - . Point de fusion : 235° C
- . Formule brute : C23H28N2O4
- . Poids moléculaire : 396,47
- . Spectre de R.M.N. (à 250 MHz ; CD3OD) δ ppm =
- . 7,83, m, CONH
- . entre 7,12 et 7,45, m, 8 protons benzéniques
- . 4,8, s, CH2 benzylique
- . 4,5, m, proton tropanique axial en 3
- . 3,88 et 3,91, s, 2 CH3O
- . 3,6, s, 2 protons tropaniques en 1 et 5
- . entre 2,5 et 2,7, m, 2 protons tropaniques axiaux en 2 et 4 et 2 protons tropaniques en 6 et 7
- . 2,13, m, 2 protons tropaniques équatoriaux en 2 et 4
- . 1,96, m, 2 protons tropaniques en 6 et 7
- . Melting point: 210 ° C
- . Gross formula: C 23 H 28 N 2 O 4
- . Molecular Weight: 396.47
- . NMR spectrum (at 250 MHz; CD 3 OD) δ ppm =
- . between 7.05 and 7.65, m, (8 benzene protons and CONH)
- . 4.5, m, axial proton in 3
- . 4.42, s, -CH 2 benzyl
- . 3.82 and 3.88, s, 2 CH 3 0
- . 3.53, s, 2 tropanic protons in 1 and 5
- . 2.5, m, axial tropic protons in 2 and 4 and 2 tropic protons in 6 and 7
- . 2.25, m, 2 tropanic protons in 6 and 7
- 1.92, m, 2 equatorial tropanic protons in 2 and 4
then (b) 1.2 g (17%) of the equatorial N-oxide (Ib) (code number 2) which is recrystallized from ethyl ether: - . Melting point: 235 ° C
- . Gross formula: C 23 H 28 N 2 O 4
- . Molecular Weight: 396.47
- . NMR spectrum (at 250 MHz; CD 3 OD) δ ppm =
- . 7.83, m, CONH
- . between 7.12 and 7.45, m, 8 benzene protons
- . 4.8, s, CH 2 benzyl
- . 4.5, m, axial tropic proton in 3
- . 3.88 and 3.91, s, 2 CH 3 O
- . 3.6, s, 2 tropanic protons in 1 and 5
- . between 2.5 and 2.7, m, 2 axial tropic protons in 2 and 4 and 2 tropic protons in 6 and 7
- . 2.13, m, 2 equatorial tropanic protons in 2 and 4
- . 1.96, m, 2 tropanic protons in 6 and 7
② A une solution à 20° C de 26 g deβ-(diméthoxy-2,3) benzoyl amino-3 N-benzyl aza-8 bicyclo [3.2.1] octane (II) dans 300 ml d'acétonitrile, on ajoute lentement 150 ml d'eau oxygénée à 120 volumes. Puis on porte le mélange 30 minutes au reflux. Après refroidissement on ajoute du palladium sur charbon à 5 %, humide, pour détruire l'excès d'eau oxygénée. Puis on filtre, évapore le filtrat et chromatographie le résidu sur colonne de silice (chromatographie liquide à moyenne pression). Par élution par le mélange chlorure de méthylène 95 % - méthanol 5 %, on obtient 9 g (33 %) de N-oxyde axial [(Ia), numéro de code 1J, puis par élution par le mélange chlorure de méthylène 85 % - méthanol 15 %, on obtient 9 g (33 %) de N-oxyde équatorial [(Ib), numéro de code 2] identiques pour les spectres RMN aux produits obtenus par la méthode ①.② To a solution at 20 ° C of 26 g of β- (2,3-dimethoxy) 3-amino benzoyl N-benzyl aza-8 bicyclo [3.2.1] octane (II) in 300 ml of acetonitrile, slowly added 150 ml of hydrogen peroxide at 120 volumes. Then the mixture is brought to reflux for 30 minutes. After cooling, 5% palladium on charcoal, wet, is added to destroy the excess hydrogen peroxide. Then filtered, the filtrate is evaporated and the residue is chromatographed on a silica column (medium pressure liquid chromatography). By elution with a 95% methylene chloride - 5% methanol mixture, 9 g (33%) of axial N-oxide [(Ia), code number 1J are obtained, then by elution with a 85% methylene chloride mixture - 15% methanol, 9 g (33%) of equatorial N-oxide [(Ib), code number 2] identical for the NMR spectra to the products obtained by the method ① are obtained.
Nous noterons ici que l'attribution axiale et équatoriale des N-oxydes (Ia) et (Ib) a été faite selon l'étude RMN des N-oxydes tropaniques décrite dans Helvetica Chimica Acta. 55, 637, (1972).We note here that the axial and equatorial attribution of the N-oxides (Ia) and (Ib) was made according to the NMR study of the tropanic N-oxides described in Helvetica Chimica Acta. 55, 637, (1972).
Par les mêmes procédés ① ou ② précédemment décrits, mais à partir des réactifs correspondants, on obtient les composés de formule (I) de numéros de code 3 à 8, 13 à 16, 18 et 19 répertoriés dans le tableau I suivant.
Les composés selon l'invention ont été étudiés chez l'animal de laboratoire et ont montré une activité sur le système nerveux central, notamment une action neuroleptique.The compounds according to the invention have been studied in laboratory animals and have shown activity on the central nervous system, in particular a neuroleptic action.
Ces propriétés psychotropes ont été mises en évidence chez la souris, notamment par le test de l'antagonisme aux redressements à l'apomorphine réalisé d'après le protocole décrit par G. GOURET et Coll. dans J. Pharmacol. (Paris) (1973), 4, 341.These psychotropic properties have been demonstrated in mice, in particular by the test of antagonism to rectifications with apomorphine carried out according to the protocol described by G. GOURET and Coll. in J. Pharmacol. (Paris) ( 1973 ), 4, 34 1 .
La toxicité aiguë des composés selon l'invention a également été étudiée chez la souris par voie intrapéritonéale. Le tableau II ci-après donne à titre d'exemple non limitatif les résultats obtenus avec certains des composés selon l'invention.
Comme le montre le tableau ci-dessus, l'écart entre les doses toxiques et les doses actives permet l'emploi comme médicaments des composés (I), notamment dans le traitement des troubles du psychisme, notamment comme neuroleptiques.As shown in the table above, the difference between the toxic doses and the active doses allows the use of the compounds (I) as medicaments, in particular in the treatment of mental disorders, in particular as neuroleptics.
La présente invention a donc également pour objet, à titre de médicaments, les composés de formule (I) pharmaceutiquement acceptables. L'invention s'étend aux compositions pharmaceutiques renfermant, à titre de principe actif, l'un au moins des médicaments définis ci-dessus, en association avec un véhicule pharmaceutiquement acceptable.The present invention therefore also relates, as medicaments, to the compounds of formula (I) which are pharmaceutically acceptable. The invention extends to pharmaceutical compositions containing, as active principle, at least one of the medicaments defined above, in combination with a pharmaceutically acceptable vehicle.
Ces compositions peuvent être administrées en particulier (a) par voie orale sous forme de comprimés, dragées ou gélules contenant chacun jusqu'à 300 mg de principe actif (jusqu'à 8 comprimés, dragées ou gélules par jour) ou sous forme de solution contenant de 0,1 à 1 % de principe actif (jusqu'à 60 gouttes, une à trois fois par jour) ou (b) par voie parentérale sous forme d'ampoules injectables contenant chacune jusqu'à 100 mg de principe actif (jusqu'à 8 ampoules par jour).These compositions can be administered in particular (a) orally in the form of tablets, dragees or capsules each containing up to 300 mg of active principle (up to 8 tablets, dragees or capsules per day) or in the form of a solution containing 0.1 to 1% of active ingredient (up to 60 drops, one to three times a day) or (b) parenterally in the form of injectable ampoules each containing up to 100 mg of active ingredient (up to 8 vials per day).
Claims (12)
R3 pouvant en outre représenter un groupe NH2 ou NH-alkyl. en C1-C4 quand R4 = halogène et un atome d'hydrogène quand R4 représente un groupe OH ou alkyloxy en C1-C4;
R 3 can also represent an NH 2 or NH-alkyl group. in C 1 -C 4 when R 4 = halogen and a hydrogen atom when R 4 represents an OH or C 1 -C 4 alkyloxy group;
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8308350A FR2546169B1 (en) | 1983-05-20 | 1983-05-20 | N-OXIDES OF AMINOCYCLIC DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR APPLICATION IN THERAPEUTICS |
FR8308350 | 1983-05-20 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0127529A2 true EP0127529A2 (en) | 1984-12-05 |
EP0127529A3 EP0127529A3 (en) | 1987-10-14 |
Family
ID=9289014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP84401032A Withdrawn EP0127529A3 (en) | 1983-05-20 | 1984-05-18 | Aminocyclic n-oxide derivatives, process for their preparation and their therapeutical use |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0127529A3 (en) |
JP (1) | JPS6034966A (en) |
AU (1) | AU2799484A (en) |
ES (1) | ES532644A0 (en) |
FR (1) | FR2546169B1 (en) |
ZA (1) | ZA843757B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4803199A (en) * | 1982-06-29 | 1989-02-07 | Peter Donatsch | Pharmaceutically useful heterocyclic and carbocyclic acid esters and amides of alkylene bridged piperidines |
WO2010113065A1 (en) | 2009-03-28 | 2010-10-07 | Braun Gmbh | Gripping area for a working device |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE456502T1 (en) | 2003-09-10 | 2010-02-15 | Hitachi Construction Machinery | CONSTRUCTION MACHINERY |
Citations (8)
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---|---|---|---|---|
EP0013138A1 (en) * | 1978-12-30 | 1980-07-09 | Beecham Group Plc | Azabicycloalkyl derivatives, a process for their preparation and pharmaceutical compositions containing them |
GB2042522A (en) * | 1979-01-16 | 1980-09-24 | Delalande Sa | Nor-tropane derivatives a process for preparing same and their application in therapeutics |
GB2088364A (en) * | 1980-11-07 | 1982-06-09 | Delalande Sa | Derivatives of nortropane and granatane |
FR2499570A1 (en) * | 1981-02-11 | 1982-08-13 | Delalande Sa | 3-Acylamino-8-arylmethyl-nortropane derivs. - useful as neuroleptic agents (NL 18.7.80) |
EP0068700A1 (en) * | 1981-06-29 | 1983-01-05 | Beecham Group Plc | Azobicycloalkylbenzamides, process for their preparation and pharmaceutical compositions containing them |
EP0083737A1 (en) * | 1981-12-15 | 1983-07-20 | Beecham Group Plc | N-azabicycloalkane benzamides, process for their preparation and pharmaceutical compositions containing them |
EP0095262A1 (en) * | 1982-05-11 | 1983-11-30 | Beecham Group Plc | Azabicycloalkane derivatives, their preparation and medicaments containing them |
EP0096524A2 (en) * | 1982-06-04 | 1983-12-21 | Beecham Group Plc | Bicyclic benzamides or anilides, process for their preparation, and pharmaceutical compositions containing them |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1586468A (en) * | 1976-10-29 | 1981-03-18 | Anphar Sa | Piperidine derivatives |
GB1575310A (en) * | 1976-11-16 | 1980-09-17 | Anphar Sa | Piperidine derivatives |
GB1574418A (en) * | 1976-11-16 | 1980-09-03 | Anphar Sa | Piperidine derivatives |
-
1983
- 1983-05-20 FR FR8308350A patent/FR2546169B1/en not_active Expired
-
1984
- 1984-05-14 AU AU27994/84A patent/AU2799484A/en not_active Abandoned
- 1984-05-18 ZA ZA843757A patent/ZA843757B/en unknown
- 1984-05-18 EP EP84401032A patent/EP0127529A3/en not_active Withdrawn
- 1984-05-18 ES ES532644A patent/ES532644A0/en active Granted
- 1984-05-19 JP JP59101620A patent/JPS6034966A/en active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0013138A1 (en) * | 1978-12-30 | 1980-07-09 | Beecham Group Plc | Azabicycloalkyl derivatives, a process for their preparation and pharmaceutical compositions containing them |
GB2042522A (en) * | 1979-01-16 | 1980-09-24 | Delalande Sa | Nor-tropane derivatives a process for preparing same and their application in therapeutics |
GB2088364A (en) * | 1980-11-07 | 1982-06-09 | Delalande Sa | Derivatives of nortropane and granatane |
FR2499570A1 (en) * | 1981-02-11 | 1982-08-13 | Delalande Sa | 3-Acylamino-8-arylmethyl-nortropane derivs. - useful as neuroleptic agents (NL 18.7.80) |
EP0068700A1 (en) * | 1981-06-29 | 1983-01-05 | Beecham Group Plc | Azobicycloalkylbenzamides, process for their preparation and pharmaceutical compositions containing them |
EP0083737A1 (en) * | 1981-12-15 | 1983-07-20 | Beecham Group Plc | N-azabicycloalkane benzamides, process for their preparation and pharmaceutical compositions containing them |
EP0095262A1 (en) * | 1982-05-11 | 1983-11-30 | Beecham Group Plc | Azabicycloalkane derivatives, their preparation and medicaments containing them |
EP0096524A2 (en) * | 1982-06-04 | 1983-12-21 | Beecham Group Plc | Bicyclic benzamides or anilides, process for their preparation, and pharmaceutical compositions containing them |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4803199A (en) * | 1982-06-29 | 1989-02-07 | Peter Donatsch | Pharmaceutically useful heterocyclic and carbocyclic acid esters and amides of alkylene bridged piperidines |
US4910207A (en) * | 1982-06-29 | 1990-03-20 | Peter Donatsch | Method of treating psychosis with N-quinuclidinyl-benzamides |
US5017582A (en) * | 1982-06-29 | 1991-05-21 | Sandoz Ltd. | Method of inducing a serotonin M receptor antagonist effect with N-quinuclidinyl-benzamides |
WO2010113065A1 (en) | 2009-03-28 | 2010-10-07 | Braun Gmbh | Gripping area for a working device |
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Publication number | Publication date |
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FR2546169A1 (en) | 1984-11-23 |
AU2799484A (en) | 1984-11-22 |
FR2546169B1 (en) | 1986-03-21 |
ZA843757B (en) | 1985-01-30 |
ES8506310A1 (en) | 1985-07-01 |
ES532644A0 (en) | 1985-07-01 |
JPS6034966A (en) | 1985-02-22 |
EP0127529A3 (en) | 1987-10-14 |
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